Early in 1981, two case-control epidemiologic reports were published which implicated coffee as a risk factor for cancer of the exocrine pancreas. Considerable controversy has arisen concerning the methodology and interpretation of both of these two recent case-control studies. Furthermore, previous epidemiologic reports of an association of coffee consumption and pancreatic cancer are difficult to interpret. There is a paucity of published animal studies that have evaluated the carcinogenic risks of coffee. These few published studies do indicate that coffee (regular brewed, instant decaffeinated and instant caffeinated) is probably not an initiator of pancreatic carciongenesis. There are no animal studies where pancreatic carcinogenesis has specifically been addressed. In view of the lack of evidence of coffee as an initiator of carcinogenesis, the hypothesis that coffee may modulate the initiation and/or postinitiation stages of chemical carcinogenesis is reasonable. That is, coffee may be a cocarcinogen or promoter. Animal models exists for the evaluation of this hypothesis. Three coffee preparations will be tested: regular grind fresh brewed coffee, instant decaffeinated coffee, and instant caffeinated coffee. The methods used will be histopathologic analysis of tissues, primarily pancreas, at the light microscpic level. Specific Aim 1 is designed to evaluate the effects of continuous exposure to coffee and multiple exposures to azaserine on pancreatic carcinogenesis in the rat. If coffee enhances pancreatic carcinogenesis, then Specific Aims 2, and 3 will be pursued; otherwise, Specific Aim 4 will be pursued. Specific Aim 2 is to evaluate coffee as a cocarcinogen in the rat-azaserine model. Specific Aim 3 is to evaluate coffee as a promoter of pancreatic carcinogenesis in the rat-azaserine model. In Specific Aim 1, 2 and 3, the number and size of azaserine-induced precancerous pancreatic lesions will be determined. In Specific Aim 4, the effects of continuous exposure to coffee and multiple injections of N-nitroso-bis(2-oxopropyl)amine (BOP) on pancreatic carcinogenesis in the hamster will be examined. The incidence and multiplicity of precancerous and cancerous lesions will be determined.